Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

The occurrence of obstructive vs absorptive hydrocephalus in newborns and infants: relevance to treatment choices

Background and objective The classification of hydrocephalus in newborns and in infants is different from the classification in adulthood. This difference exists due to disparity in the source pathologies that produce the hydrocephalus, and the practical distinctions in prognosis and treatment choices. The objective of this paper is to present the spectrum of obstructive-communicating hydrocephalus, which is more complex in the pediatric group, and to propose the relevance of this particular classification to treatment options. Materials and methods The authors categorized infants with active hydrocephalus at time of presentation into the following four groups along the spectrum of communicating vs obstructive HCP. Group 1: patients with a purely absorptive (communicating) HCP. In these patients, tetraventricular dilatation is usually observed with occasional extraaxial fluid accumulation. An extracranial CSF diversion (shunt) is the treatment of choice. Group 2: patients with an obstructive component together with a persistent absorptive component. In these patients, a technically successful endoscopic procedure will not prevent progression of clinical symptoms of HCP. An extracranial CSF diversion (shunt) should be the treatment of choice even though some of these patients are currently treated by endoscopy. Group 3: patients with an obstructive component together with a temporary absorptive component. In these patients, a technically successful ETV should be followed by temporary CSF drainage [via LP, continuous spinal drainage (CLD), or ventriculostomy] with or without supplemental medical treatment (i.e., Diamox) for several days. Such temporary drainage may decrease failure rate in this subgroup. Group 4: patients with a purely obstructive HCP. In these patients, an endoscopic procedure (ETV) is the treatment of choice. According to this spectrum classification, the authors classify different entities with representative cases and discuss relevancy to treatment options and prognosis. Results The data suggest that obstructive hydrocephalus in the very young population may be rather a combination of obstructive and absorptive problem. The outcome of the patient depends mainly not only on the basic pathology causing the hydrocephalus but also on the treatment that is chosen and its complications. While bleeding and infection represent the major causes for communicating hydrocephalus, patients with complex pathologies of congenital type and intra- or interventricular obstructions may reflect obstructive hydrocephalus. Treatment of these patients may be successful by shuntless procedures if the absorptive problem is not the major component. In transient absorptive hydrocephalus, temporary measures were effective in many cases leading to successful procedures of ETV and/or posterior-fossa decompression in selected cases. Conclusions Shuntless procedures are the dream of a pediatric neurosurgeon provided it solves the problem and does not imply unacceptable risk. However, the benefit has to be evaluated years after the procedure is performed, as only prospective multicenter studies will truly show which procedure may have the best overall results in the developing child. Until such studies are available, understanding the basic pathology or the combination of pathologies leading to hydrocephalus in a given child may open the window of opportunities for other than shunt surgery in many hydrocephalic children with major obstructive component.     

Fine needle aspiration biopsy for skull tumors: technical note and two demonstrative case reports.

Fine needle aspiration biopsy was performed in two case of infiltrating skull lesions. The role played by this relatively simple procedure in avoiding a major operation is discussed.     

Prevention of immune precipitation by purified components of the alternative pathway

The role of the alternative pathway in complement-mediated prevention of immune precipitation has been investigated by the use of BSA-anti-BSA immune complex (IC) purified components. For immune precipitation to be prevented all six alternative pathway components (C3, factors B D, P, H and I) were required. In the absence of one or both of the control proteins H and I, excessive fluid phase turnover of C3 occurred with precipitation of IC. Kinetic studies showed that in the presence of the control proteins, an initial phase of precipitation occurred, and was followed by a phase of resolubilization of IC. When the efficiency of classical and alternative pathways in the prevention of immune precipitation was compared it was found that the classical pathway proteins were more effective than the alternative pathway components. A reaction mixture containing the components of both pathways was no better than the classical pathway protein alone. 125I-C3 was bound to IC which had been rendered soluble in the presence of classical or alternative pathway components. A molar ratio of two molecules C3b:five molecules IgG was calculated. Other complement components which were bound to IC which had been formed in the presence of serum were C1q, C4, C2, C3, C5, P and H. Factors B and I were not detected. Our findings suggest that the alternative pathway is of secondary importance to the classical pathway in the prevention of immune precipitation.     

Platelet activation in psoriasis

Recent epidemiological studies have suggested that psoriasis represents a risk factor for thrombotic vascular diseases. In order to evaluate the possible role of hemostatic changes in the development of thrombotic episodes in psoriasis, some parameters of the hemostatic "balance" were investigated in 22 male psoriatic patients and compared to those of 22 male control subjects. Incidence of known risk factors for vascular diseases (diabetes, hypertension, smoking, dyslipidemia) was comparable in the two study groups. There were no statistically significant differences in platelet count, circulating platelet aggregates, platelet production of malondialdehyde (MDA), total plasma antithrombin and fibrinolytic activities. In patients with psoriasis the incidence of spontaneous platelet hyperaggregability and plasma levels of beta-thromboglobulin were significantly higher than in control subjects. Platelet regeneration time, measured as MDA recovery after aspirin ingestion, was significantly shorter in psoriatic patients. These data suggest that an in vivo platelet activation occurs in patients with psoriasis and could contribute to the development of thrombotic complications. The release of mitogenic and inflammatory substances by activated platelets may play a role in the histogenesis of psoriatic lesions.     

Glucocorticoid blockade does not abrogate tumor-induced cachexia

Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating glucocorticoids and interleukin-6 (IL-6) have been observed in cancer patients with cachexia and are implicated as major mediators in this process. The purpose of this study was to investigate the role of circulating glucocorticoid levels as primary mediators in cancer-induced cachexia. We evaluated whether inhibition of glucocorticoids with the receptor antagonist RU-486 could abrogate the detrimental wasting of muscle and adipose tissues seen in a well-characterized murine tumor-induced cachexia model. Mice (12/group) were randomized to control, tumor-bearing, control + vehicle, or tumor-bearing + glucocorticoid receptor antagonist groups. Circulating serum glucocorticoid and IL-6 levels were measured in addition to multiple body composition parameters, such as total body weight, lean body mass, and adipose content. The results of this study indicate a significant physiological alteration in the tumor-bearing host that causes severe and detrimental changes in body composition parameters. Regression analysis demonstrated a significant correlation between increased circulating glucocorticoid levels and alterations in body composition parameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the untoward effects of tumor-induced cachexia are not mediated primarily by the peripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.     

Biological Evidence for a Neurodevelopmental Model of Pediatric Bipolar Disorder

Bipolar disorder (BD) is a chronic illness with high morbidity and mortality. Pediatric onset BD has a more severe course of illness with higher rates of relapse and psychosocial impairment. Discovering interventions early in the course of BD in youth is paramount to preventing full illness expression and improve functioning in these individuals throughout the lifespan. It is therefore important to understand the mechanisms involved in the development of BD in order to determine which youth are at most risk and provide biological targets for early intervention. To serve this cause, we propose a neurodevelopmental model of BD, based on the existing data that implicate prefrontal - subcortical network dysfunction, caused by pre-existing genetic susceptibility and triggered by pathological reactions to stress and chronic inflammatory processes.     

Mortality in bullous pemphigoid: A systematic review and meta‐analysis of standardized mortality ratios

There are inconsistent data on mortality rates in patients with bullous pemphigoid (BP). Trends in mortality in BP throughout the years are yet to be established. The aim of the present study was to study the mortality in BP patients relative to the general population and to estimate trends in standardized mortality over the past 30 years. We performed a systematic review and meta‐analysis of observational studies in Medline, Embase and Scopus (1823–2017). Reference lists of included studies were also searched for eligible studies. Quality of evidence was assessed using the Newcastle–Ottawa Scale (NOS). A meta‐analysis was performed using random‐effects models to estimate pooled standardized mortality ratios (SMR) with 95% confidence intervals (CI). Meta‐regression models were used to investigate the secular trends in SMR. Ten studies were included covering the period 1960–2015 (1736 patients, 746 deaths). Pooled all‐cause SMR was 3.6 (95% CI, 2.6–5.0). There was no trend in all‐cause SMR across the last three decades (regression coefficient 0.02 [change in logSMR/year]; 95% CI, 0.04–0.08; P = 0.545). In conclusion, there is a 3.6‐fold increased mortality among patients with BP as compared with the age‐matched general population. The excess mortality in BP has not changed significantly over the past 30 years.